Description: (Applicant's Description) We have established the first practical murine model of the most common human cancer-basal cell carcinomas-by exposing the skin of ptc +/- mice to repeated ultraviolet light irradiation. We propose a series of experiments first to refine this model by varying the wavelength, the degree, and the frequency of irradiation. We will test several additional variables including the effects of alternative environmental insults that appear to provoke human basal cell carcinomas-ionizing irradiation and arsenic as well as chemical carcinogens. We will validate the utility of this model by assessing chemopreventive agents that have been studied on humans-retinoids, green tea aqueous extract, and low-fat diet and then will utilize the model to test for chemopreventive efficacy of tea preparations and inhibitors of COX-1 and of COX-2. We will also assess the influence of varied genetic backgrounds both on photoinduction of efficacy of chemopreventive agents. Lastly, we will survey human extracutaneous cancers aberrant hedgehog pathway signaling.